title: Cutaneous tactile allodynia associated with microvascular dysfunction in muscle.
abstract: BACKGROUND
  Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia.
  
  
  RESULTS
  Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist.
  
  
  CONCLUSIONS
  Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.
authors.affiliation: Department of Anesthesia, McGill University, Montreal, Quebec, Canada. andre.laferriere@mcgill.ca
authors.forename: Andre
authors.initials: A
authors.lastname: Laferrière
authors.forename: Magali
authors.initials: M
authors.lastname: Millecamps
authors.forename: Dimitris N
authors.initials: DN
authors.lastname: Xanthos
authors.forename: Wen Hua
authors.initials: WH
authors.lastname: Xiao
authors.forename: Chiang
authors.initials: C
authors.lastname: Siau
authors.forename: Marissa
authors.initials: M
authors.lastname: de Mos
authors.forename: Christelle
authors.initials: C
authors.lastname: Sachot
authors.forename: J Vaigunda
authors.initials: JV
authors.lastname: Ragavendran
authors.forename: Frank Jpm
authors.initials: FJ
authors.lastname: Huygen
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bennett
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Coderre
mesh_terms: D000818:Animals; D007511:Ischemia; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D012879:Skin Physiological Phenomena; D055698:Touch Perception